Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum

Autor:	Asim B. Abdel-Mageed, Laith Alzweri, Brian Dick, Ecem Kaya-Sezginer, Wayne Jg Hellstrom, Serap Gur, Suresh C. Sikka, Didem Yilmaz-Oral, Cetin Volkan Oztekin
Rok vydání:	2020
Předmět:	Male medicine.medical_specialty Nitric Oxide Synthase Type III Hormone Replacement Therapy Urology Endocrinology Diabetes and Metabolism Penile Induration Nitric Oxide Synthase Type I Nitric Oxide Sildenafil Citrate Nitric oxide chemistry.chemical_compound Endocrinology Erectile Dysfunction Western blot Enos Internal medicine medicine Humans Testosterone Cyclic GMP Cyclic guanosine monophosphate Phenylephrine Cyclic Nucleotide Phosphodiesterases Type 5 biology medicine.diagnostic_test Middle Aged medicine.disease biology.organism_classification Erectile dysfunction Reproductive Medicine chemistry cGMP-specific phosphodiesterase type 5 Penis medicine.drug
Zdroj:	Andrology. 8:1824-1833
ISSN:	2047-2927 2047-2919
Popis:	Background Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non-genomic pathway has been reported; however, the in vitro modulating effects of T on human corpus cavernosum (HCC) have not been studied. Objectives To compare the effects of various concentrations of T on nitric oxide (NO)-dependent and nitric oxide-independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO/cyclic guanosine monophosphate (cGMP) pathway. Materials and methods Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n = 9). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150 ng/dL), eugonadal (400 ng/dL), and hypergonadal (600 ng/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite/nitrate (NOx) assays. Results Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil-induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression. Conclusion This study reveals an important role of short-term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.
Databáze:	OpenAIRE
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